Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome

Significance Inherited or acquired defects in mitochondria lead to devastating disorders for which we have no effective general therapies. We recently reported that breathing normobaric 11% O 2 prevents neurodegeneration in a mouse model of a pediatric mitochondrial disease, Leigh syndrome. Here we provide updated survival curves of mice treated with varying doses of oxygen and explore eventual causes of death. We explore alternative hypoxia regimens and report that neither intermittent nor moderate hypoxia regimens suffice to prevent neurological disease. Finally, we show that hypoxia can not only prevent, but also reverses the brain lesions in mice with advanced neuropathology. Our preclinical studies will help guide future clinical studies aimed at harnessing hypoxia as a safe and practical therapy.